Suicide and fatal antidepressant poisoning.
Questionnaires were sent to ophthalmologists (850) and neurologists (434) in the United Kingdom. Estimated numbers of patients seen with acquired nystagmus, treatment options used, and the results of treatment of the patients were collected.
A number of studies in the past have indicated that certain types of dopamine receptor-mediated behaviours can be reversed by serotonin agonists. We have recently described a behavior in neonatal rats induced by the selective D1 receptor agonist SKF 38393, which we termed vacillatory behavior. The current study was aimed at determining the effectiveness of several serotonin-specific agents at reversing this behavior. Behaviors measured on day 15 revealed that SKF 38393-mediated behavior was effectively blocked by SCH 23390 (a selective D1 antagonist), serotonin receptor agonists specific for the 5-HT1A receptor (buspirone and ipsapirone), and the serotonin uptake inhibitor clomipramine. However, the behavior was not reversed by diazepam. These data suggest that the serotonergic and dopaminergic neurotransmitter systems must be in a proper balance for appropriate decision-making behaviors to occur.
Respiratory dysfunction after cervical spinal cord injury (SCI) has not been examined experimentally using conscious animals, although clinical SCI most frequently occurs in midcervical segments. Here, we report a C5 hemicontusion SCI model in rats with abnormalities that emulate human post-SCI pathophysiology, including spontaneous recovery processes. Post-C5 SCI rats demonstrated deficits in minute ventilation (Ve) responses to a 7% CO2 challenge that correlated significantly with lesion severities (no injury or 12.5, 25, or 50 mm x 10 g weight drop; New York University impactor; p < 0.001) and ipsilateral motor neuron loss (p = 0.016). Importantly, C5 SCI resulted in at least 4 weeks of respiratory abnormalities that ultimately recovered afterward. Because serotonin is involved in respiration-related neuroplasticity, we investigated the impact of activating 5-HT1A receptors on post-C5 SCI respiratory dysfunction. Treatment with the 5-HT1A agonist 8-hydroxy-2-(di-n-propylmino)tetralin (8-OH DPAT) (250 microg/kg, i.p.) restored hypercapnic Ve at 2 and 4 weeks after injury (i.e., approximately 39.2% increase vs post-SCI baseline; p < or = 0.033). Improvements in hypercapnic Ve response after single administration of 8-OH DPAT were dose dependent and lasted for approximately 4 h(p < or = 0.038 and p < or = 0.024, respectively). Treatment with another 5-HT1A receptor agonist, buspirone (1.5 mg/kg, i.p.), replicated the results, whereas pretreatment with a 5-HT1A-specific antagonist, 4-iodo-N-[2-[4(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (3 mg/kg, i.p.) given 20 min before 8-OH DPAT negated the effect of 8-OH DPAT. These results imply a potential clinical use of 5-HT1A agonists for post-SCI respiratory disorders.
Results showed that buspirone (20 mg/kg, i.p.) decreased significantly haloperidol-induced catalepsy and balance disorder in a dose dependent manner. Furthermore, 8-OH-DPAT (10 mg/kg, i.p.), as an agonist of 5-HT(1A) receptor, decreased haloperidol-induced catalepsy and balance disorder. The effect of buspirone (20 mg/kg, i.p.) on haloperidol-induced motor disorders was abolished by NAN-190 (10 mg/kg, i.p.), as a 5-HT(1A) receptor antagonist. From the results it may be concluded that buspirone improves haloperidol-induced catalepsy and balance disorder through activation of 5-HT(1A) receptors.
As noted previously, it is likely that the tendency to lash out verbally or physically at others is influenced by an interaction among multiple complex biologic factors. We need to investigate how these systems interact with each other to develop a more thorough understanding of the brain's influence over aggressive behavior. We are at a very early stage in our understanding of the neurobiology of aggression. There are no simple tools for studying the complex neurophysiology of the human brain. The studies cited in this article include techniques limited in their utility. As our technologies improve, discovering a more thorough picture of the brain's influence over aggressive behavior may be possible. For example, functional neuroimaging may help to localize abnormal neurotransmitter functioning in the brains of individuals with impulsive aggressive behavior. Our technologies are beginning to reveal the differential effects of subsystems of neurotransmitter regulation. Subtypes of serotonin receptors may differentially mediate impulsive aggressive behaviors. Animal studies suggest that 5-HT 1A receptor stimulation results in a decrease in aggressive behavior. As noted previously, aggressive personality-disordered patients show a blunted prolactin response to the 5-HT1A agonist buspirone. Antagonism of 5-HT 2 receptors appears to decrease aggression, and this effect may explain the ability of newer antipsychotic agents (which, unlike older antipsychotic medications, block 5-HT 2 receptors) to produce a dramatic reduction in aggression and agitation independent of effects on psychotic symptoms. Neglecting psychosocial factors in the causes of aggressive behavior would also be naive. Although environmental factors account for much of the predisposition to aggression, there have been few systematic studies to explore the relationship between life experiences and aggression. In addition, there have been no well-designed studies of the interaction between biology and an individual's environment in the genesis of aggressive behavior. There is some evidence of an association between childhood abuse and neglect and adult antisocial personality disorder, but this relationship might be merely an artifact of the genetic relationship between parental and offspring antisocial personality disorder. As we discussed in the introduction, one of the biggest hurdles in the study of the neurobiology of aggression is the lack of a consensus on definitions. "Intermittent Explosive Disorder" is the only category in DSM-IV that directly addresses individuals with problems with aggression, but the criteria are vague and only focus on a handful of the many patients who exhibit problems with aggressive behavior. It is our hope that investigators in this field can work together toward developing more precise and encompassing diagnostic criteria to study effectively both the neurobiology and treatment of these disorders.